A network meta-analysis evaluating the efficacy and safety of adjuvant therapy after nephrectomy in renal cell carcinoma.

BACKGROUND: In the past few years, there has been a continuous rise in the occurrence of renal cell carcinoma (RCC), with RCC recurrence becoming the primary factor behind fatalities. Despite numerous clinical trials, the impact of different medications on the long-term survival of patients with RCC after surgery remains uncertain. This network meta-analysis aimed to evaluate the impact of various medications on the survival and safety of drugs in individuals with RCC following nephrectomy. METHODS: We conducted a thorough search in various databases, including CNKI, WAN FANG DATA, VIP, Web of Science, Cochrane Library (CENTRAL), PubMed, Scopus, and Embase, for articles published prior to June 2, 2023. This meta-analysis incorporated randomized controlled trials (RCTs). RESULTS: The analysis included 17 studies with 14,298 participants. The findings from the disease-free survival (DFS) analysis indicated that pembrolizumab demonstrated efficacy in enhancing DFS among patients with RCC following nephrectomy when compared to the placebo group (HR = 0.83, 95%CI 0.70 to 0.99). None of the drugs included in the study significantly improved overall survival (OS) and recurrence-free survival (RFS) after nephrectomy. For adverse events (AEs), sorafenib, pazopanib, sunitinib, and nivolumab plus ipilimumab interventions showed a higher incidence of adverse events compared with placebo. CONCLUSION: The network meta-analysis yielded strong evidence indicating that pembrolizumab could potentially enhance DFS in patients with RCC following nephrectomy, surpassing the effectiveness of a placebo.

Mendelian randomization analysis reveals a protective association between genetically predicted systemic lupus erythematosus and renal cell carcinoma.

Observational studies have suggested that there may be a connection between systemic lupus erythematosus (SLE) and a higher likelihood of developing urological cancers, although the exact cause-effect relationship is still unclear. This study therefore investigated the causal relationship between SLE and urological cancers using the Mendelian randomization (MR) approach. Our primary MR analysis involved using the inverse variance weighted method, which employed an inverse-variance-weighted approach, to examine the causal relationship between SLE and urological conditions. In addition, we performed various sensitivity analyses, such as MR-Egger regression, tests for heterogeneity, and leave-one-out sensitivity tests, to assess the reliability of our results. The findings from our analysis using Two-Sample MR showed that genetically predicted SLE was linked to a reduced likelihood of developing renal cell carcinoma (RCC) (odds ratio = 0.9996, 95% confidence interval = 0.9993-0.9999, P value = .0159). These results suggest a possible protective impact of SLE against RCC. Nevertheless, no substantial correlation was detected between SLE and the likelihood of developing bladder cancer or prostate cancer. Collectively, these findings offer significant fresh perspectives on the possible correlation between SLE and genitourinary malignancies, specifically RCC, which will provide ideas and basis for the treatment of RCC.

Progress of Dispersants for Coal Water Slurry.

Dispersants, serving as an essential raw material in the formulation of coal water slurry, offer an economical and convenient solution for enhancing slurry concentration, thus stimulating significant interest in the development of novel and efficient dispersants. This paper intends to illuminate the evolution of dispersants by examining both the traditional and the newly conceived types and elaborating on their respective mechanisms of influence on slurry performance. Dispersants can be classified into anionic, cationic, amphoteric, and non-ionic types based on their dissociation properties. They can be produced by modifying either natural or synthetic products. The molecular structure of a dispersant allows for further categorization into one-dimensional, two-dimensional, or three-dimensional structure dispersants. This document succinctly outlines dispersants derived from natural products, three-dimensional structure dispersants, common anionic dispersants such as lignin and naphthalene, and amphoteric and non-ionic dispersants. Subsequently, the adsorption mechanism of dispersants, governed by either electrostatic attraction or functional group effects, is elucidated. The three mechanisms through which dispersants alter the surface properties of coal, namely the wetting dispersion effect, electrostatic repulsion effect, and steric hindrance effect, are also explained. The paper concludes with an exploration of the challenges and emerging trends in the domain of dispersants.

Revealing the mechanism of quinoa on type 2 diabetes based on intestinal flora and taste pathways.

To investigate the antidiabetic effects and mechanisms of quinoa on type 2 diabetes mellitus (T2DM) mice model. In this context, we induced the T2DM mice model with a high-fat diet (HFD) combined with streptozotocin (STZ), followed by treatment with a quinoa diet. To explore the impact of quinoa on the intestinal flora, we predicted and validated its potential mechanism of hypoglycemic effect through network pharmacology, molecular docking, western blot, and immunohistochemistry (IHC). We found that quinoa could significantly improve abnormal glucolipid metabolism in T2DM mice. Further analysis showed that quinoa contributed to the improvement of gut microbiota composition positively. Moreover, it could downregulate the expression of TAS1R3 and TRPM5 in the colon. A total of 72 active components were identified by network pharmacology. Among them, TAS1R3 and TRPM5 were successfully docked with the core components of quinoa. These findings confirm that quinoa may exert hypoglycemic effects through gut microbiota and the TAS1R3/TRPM5 taste signaling pathway.

Xiaozheng pill exerts an anti-mammary hyperplasia effect through Raf/ERK/ELK and HIF-1α/bFGF pathways.

Background and aim: The purpose of this study is to explore whether the Xiaozheng pill (XZP) has the effect of anti-hyperplasia of mammary glands (HMG) and to identify the related signaling pathways. Experimental procedure: We analyzed the effective chemical components of the XZP, as well as the key chemical components, key proteins, main biological processes, and pathways in the treatment of HMG; Secondly, the levels of Estradiol (E2), Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Progesterone (P), Raf/ERK/ELK and HIF-1α/bFGF pathways related proteins were detected; Finally, the effect of XZP on metabolites was analyzed by metabolomics. Results and conclusion: In this study, we identified key targets and pathways for XZP therapy of HMG, including EGFR, VEGFA, ER, and Ras signaling pathways. Animal experiments show that XZP can reduce the levels of E2, LH, and FSH and increase the expression of P in HMG mice. XZP can restore the normal structure of breast tissue and reduce ERα, ERß, and PR expression in breast tissue. In addition, metabolomics results show that XZP also regulates HMG metabolites, including HIF-1α and metabolic pathways. The Western blot results showed that XZP intervention can reduce the protein expression of p-Raf1, Raf1, p-ERK1/2, ERK1/2, ELK, HIF-1α, and bFGF in the breast tissue of HMG mice. XZP may eliminate abnormal breast hyperplasia through inhibition of apoptosis and angiogenesis, which may be linked with the regulation of the Raf/ERK/ELK and HIF-1α/bFGF signaling pathways in HMG mice. These results suggest that XZP treatment may be beneficial for the management of HMG.

Moringa oleifera leaf supplementation relieves oxidative stress and regulates intestinal flora to ameliorate polycystic ovary syndrome in letrozole-induced rats.

This study investigated the effects of supplementation Moringa oleifera leaf (MOL) on relieving oxidative stress, anti-inflammation, changed the relative abundance of multiple intestinal flora and blood biochemical indices during letrozole-induced polycystic ovary syndrome (PCOS). Previous studies have shown that MOL has anti-inflammatory, anti-oxidation, insulin-sensitizing effects. However, whether MOL has beneficial effects on PCOS remains to be elucidated. In the current study, 10-week-old female Sprague-Dawley rats received letrozole to induce PCOS-like rats, and subsequently were treated with a MOL diet. Then, the body weight and estrus cycles were measured regularly in this period. Finally, the ovarian morphology, blood biochemical indices, anti-oxidative, intestinal flora, and anti-inflammation were observed at the end of the experiment. We found that MOL supplementation markedly decreased the body weight, significantly upregulated the expression of Sirt1, FoxO1, PGC-1α, IGF1, and substantially modulated the sex hormone level and improved insulin resistance, which may be associated with the relieves oxidative stress. Moreover, the supplementation of MOL changed the relative abundance of multiple intestinal flora, the relative abundance of Fusobacterium, Prevotella were decreased, and Blautia and Parabacteroides were increased. These results indicate that MOL is potentially a supplementary medication for the management of PCOS.

MMP9 and TYROBP affect the survival of circulating tumor cells in clear cell renal cell carcinoma by adapting to tumor immune microenvironment.

Circulating tumor cells (CTCs) play a key role in tumor metastasis. CTCs have altered gene expression and can survive in the bloodstream. Finding the key genes whose expression are altered in CTCs could help explain the mechanism of tumor metastasis. We searched for genes differentially expressed in CTCs by analyzing four CTCs and primary tumor gene expression datasets in the GEO database. Key genes of clear cell renal cell carcinoma (ccRCC) CTCs were identified. The correlation between key genes and the immune microenvironment of ccRCC was explored. Finally, the CTCs cell model of ccRCC was constructed by in vivo screening method, and the expression of key genes was detected at the cell and tissue levels. A total of 771 DEGs were obtained. Gene enrichment analysis showed that DEGs of CTCs were mainly involved in the regulation of the tumor immune process and tumor cell apoptosis. Finally, we found 2 key genes, MMP9 and TYROBP in ccRCC CTCs. The high expression of these 2 genes predicted a poor prognosis of ccRCC, and the expression levels of these 2 genes were significantly increased in CTCs and ccRCC tissues. Our study suggested that genetic alterations in CTCs contribute to the ability of CTCs to survive in the blood by adapting to the tumor microenvironment. MMP9 and TYROBP are potential therapeutic and prognostic targets for ccRCC.

SERPINE1 and its co-expressed genes are associated with the progression of clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma(ccRCC) is a frequently occurring malignant tumor of the urinary system. Despite extensive research, the regulatory mechanisms underlying the pathogenesis and progression of ccRCC remain largely unknown. METHODS: We downloaded 5 ccRCC expression profiles from the Gene Expression Omnibus (GEO) database and obtained the list of differentially expressed genes (DEGs). Using String and Cytoscape tools, we determined the hub genes of ccRCC, and then analyzed their relationship with ccRCC patient survival. Ultimately, we identified SERPINE1 as a prognostic factor in ccRCC. Meanwhile, we confirmed the role of SERPINE1 in 786-O cells by cell transfection and in vitro experiments. RESULTS: Our analysis yielded a total of 258 differentially expressed genes, comprising 105 down-regulated genes and 153 up-regulated genes. Survival analysis of SERPINE1 expression in The Cancer Genome Atlas (TCGA) confirmed its association with the increase of tumor grade, lymph node metastasis, and tumor stage, as well as with shorter survival. Furthermore, we found that SERPINE1 expression levels were associated with CD8 + T cells, CD4 + T cells, B cells, macrophages, neutrophils, and dendritic cells. Cell experiments showed that knockdown SERPINE1 expression could inhibit the proliferation, migration and invasion of ccRCC cells. Among the co-expressed genes with the highest correlation, ITGA5, SLC2A3, SLC2A14, SHC1, CEBPB, and ADA were overexpressed and associated with shorter overall survival (OS) in ccRCC. CONCLUSIONS: In this study, we identified hub genes that are strongly related to ccRCC, and highlights the potential utility of overexpressed SERPINE1 and its co-expressed genes could be used as prognostic and diagnostic biomarkers in ccRCC.

Sorafenib-Loaded Cu2-xSe Nanoparticles Boost Photothermal-Synergistic Targeted Therapy against Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) accounts for the predominant form of liver malignancy and presents a leading cause of cancer-related death globally. Sorafenib (SOR), a first-line targeted drug for advanced HCC treatment, has a battery of untoward side effects. Photothermal therapy (PTT) has been utilized as an effective adjuvant in synergy with other approaches. However, little is known about the tumoricidal efficacy of combining SOR with PTT for HCC. Herein, a novel versatile nanoparticle, Cu2-xSe@SOR@PEG (CSP), that is based on a photothermal Cu2-xSe core and SOR for simultaneously reinforcing PTT and reducing the adverse effects of SOR was constructed. The synthesized CSP exhibited a remarkably enhanced therapeutic effect upon 808 nm laser irradiation via dampening HCC cell propagation and metastasis and propelling cell apoptosis. The intravenous administration of CSP substantially suppressed tumor growth in a xenograft tumor mouse model. It was noted that the CSP manifested low toxicity and excellent biocompatibility. Together, this work indicates a promising and versatile tool that is based on synergistic PTT and molecular-targeted therapy for HCC management.

Comprehensive analysis of the collagen family members as prognostic markers in clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is one of the common malignant tumors worldwide. There is still a lack of effective diagnostic and therapeutic targets for the recurrence and metastasis of ccRCC. In this study, we sought to identify effective diagnostic and therapeutic targets for ccRCC recurrence and metastasis. Methods: Gene Expression Omnibus (GEO) dataset was used to obtain differentially expressed genes (DEGs) between primary and metastasis ccRCC. We used The Cancer Genome Atlas (TCGA), GeneMANIA, cBioPortal, MethSurv, and TIMER to analyze the expression differences, mutation status, prognostic value, molecular function, and immune infiltration of hub genes in renal cell carcinoma (RCC). Results: We obtained a total of 35 different gene lists. Six collagen family members were identified as hub genes. The expression level of collagen family members was closely related to ccRCC. Moreover, differences in the expression levels of collagen family members were closely related to the stage and prognosis of ccRCC. Members of the collagen family were responsible for more than 15% of the genetic alterations in ccRCC and are involved in multiple signaling pathways. The expression level of collagen family members was closely related to the infiltration of tumor-associated immune cells. Univariate and multivariate Cox regression identified the prognosis-related genes: COL5A1. Conclusions: Our study implied that members of the collagen family may serve as a biomarker for ccRCC metastasis and prognosis.

Iridium Complex-Loaded Sorafenib Nanocomposites for Synergistic Chemo-photodynamic Therapy of Hepatocellular Carcinoma.

Although sorafenib, a multi-kinase inhibitor, has provided noteworthy benefits in patients with hepatocellular carcinoma (HCC), the inevitable side effects, narrow therapeutic window, and low bioavailability seriously affect its clinical application. To be clinically distinctive, innovative drugs must meet the needs of reaching tumor tissues and cause limited side effects to normal organs and tissues. Recently, photodynamic therapy, utilizing a combination of a photosensitizer and light irradiation, was selectively accumulated at the tumor site and taken up effectively via inducing apoptosis or necrosis of cancer cells. In this study, a nano-chemo-phototherapy drug was fabricated to compose an iridium-based photosensitizer combined with sorafenib (IPS) via a self-assembly process. Compared to the free iridium photosensitizer or sorafenib, the IPS exhibited significantly improved therapeutic efficacy against tumor cells because of the increased cellular uptake and the subsequent simultaneous release of sorafenib and generation of reactive oxygen species production upon 532 nm laser irradiation. To evaluate the effect of synergistic treatment, cytotoxicity detection, live/dead staining, cell proliferative and apoptotic assay, and Western blot were performed. The IPS exhibited sufficient biocompatibility by hemolysis and serum biochemical tests. Also, the results suggested that IPS significantly inhibited HCC cell proliferation and promoted cell apoptosis. More importantly, marked anti-tumor growth effects via inhibiting cell proliferation and promoting tumor cell death were observed in an orthotopic xenograft HCC model. Therefore, our newly proposed nanotheranostic agent for combined chemotherapeutic and photodynamic therapy notably improves the therapeutic effect of sorafenib and has the potential to be a new alternative option for HCC treatment.

Combined analysis of whole-exome sequencing and RNA sequencing in type 2 diabetes mellitus patients with thirst and fatigue.

BACKGROUND: The principal objective of this study was to gain a better understanding of the mechanisms of type 2 diabetes mellitus (T2DM) patients with fatigue (D-T2DM) through exome and transcriptome sequencing. METHODS: After whole-exome sequencing on peripheral blood of 6 D-T2DM patients, the consensus mutations were screen out and analyzed by a series of bioinformatics analyses. Then, we combined whole-exome sequencing and transcriptome sequencing results to find the important genes that changed at both the DNA and RNA levels. RESULTS: The results showed that a total of 265,393 mutation sites were found in D-T2DM patients compared with normal individuals, 235 of which were consensus mutations shared with D-T2DM patients. These genes significantly enriched in HIF-1 signaling pathway and sphingolipid signaling pathway. At the RNA level, a total of 375 genes were identified to be differentially expressed. After the DNA-RNA joint analysis, eight genes were screened that changed at both DNA and RNA levels. Among these genes, FUS and LMNA were related to carbohydrate metabolism, energy metabolism, and mitochondrial function. Subsequently, we predicted the herbs, including Qin Pi and Hei Zhi Ma, that might play a therapeutic role in D-T2DM through the SymMap database. CONCLUSION: These findings have significant implications for understanding the mechanisms of D-T2DM and provide potential targets for D-T2DM diagnosis and treatment.

Case Report: A Programmed Cell Death-1 Inhibitor-Related Abdominal Fibroinflammatory Reaction Affecting Multiple Organs in A Non-Small-Cell Lung Cancer Patient.

Immunotherapy utilizing programmed cell death-1 (PD-1)/PD-L1 inhibitors has been regarded as a rising hope for tumor patients, and their effects have been demonstrated in many clinical trials. However, immune-related adverse events also occur in patients and can sometimes have severe consequences. Pembrolizumab (Keytruda) is a humanized monoclonal anti-PD-1 antibody that has been approved by the US Food and Drug Administration for non-small-cell lung cancer. Here, we report a rare case of an abdominal fibroinflammatory reaction that affected multiple organs during anti-PD-1 immunotherapy using pembrolizumab in a non-small-cell lung cancer patient. The patient's case demonstrates that immunotherapy-related abdominal fibroinflammatory reactions need to be considered, especially for patients with a history of pre-existing conditions in the abdomen. Glucocorticoids may be useful as a treatment when a diagnosis is confirmed.

Naringenin regulates gut microbiota and SIRT1/ PGC-1ɑ signaling pathway in rats with letrozole-induced polycystic ovary syndrome.

PURPOSE: To evaluate the effect of naringenin on improving PCOS and explore the mechanism. METHODS: Firstly, we carried out differential gene expression analysis from transcriptome sequencing data of human oocyte to screen the KEGG pathway, then the PCOS-like rat model was induced by letrozole. They were randomly divided into four groups: Normal group (N), PCOS group (P), Diane-35 group (D), and Naringenin group (Nar). The changes of estrus cycle, body weight, ovarian function, serum hormone levels, glucose metabolism, along with the expression of SIRT1, PGC-1ɑ, claudin-1 and occludin of the ovary and colon were investigated. Furthermore, the composition of the gut microbiome of fecal was tested. RESULTS: By searching the KEGG pathway in target genes, we found that at least 15 KEGG pathways are significantly enriched in the ovarian function, such as AMPK signaling pathway, insulin secretion, and ovarian steroidogenesis. Interestingly, naringenin supplementation significantly reduced body weight, ameliorated hormone levels, improved insulin resistance, and mitigated pathological changes in ovarian tissue, up-regulated the expression of PGC-1ɑ, SIRT1, occludin and claudin-1 in colon. In addition, we also found that the abundance of Prevotella and Gemella was down-regulated, while the abundance of Butyricimonas, Lachnospira, Parabacteroides, Butyricicoccus, Streptococcus, Coprococcus was up-regulated. CONCLUSION: Our data suggest that naringenin exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota and SIRT1/PGC-1ɑ signaling pathway. Our research may provide a new perspective for the treatment of PCOS and related diseases.

Quinoa Reduces High-Fat Diet-Induced Obesity in Mice via Potential Microbiota-Gut-Brain-Liver Interaction Mechanisms.

The gut microbiota is important in the occurrence and development of obesity. It can not only via its metabolites, but also through microbiota-gut-brain-liver interactions, directly or indirectly, influence obesity. Quinoa, known as one kind of pseudocereals and weight loss food supplements, has been high-profile for its high nutritional value and broad applications. In this context, we produced high-fat diet-induced (HFD) obese mouse models and assessed the efficacy of quinoa with saponin and quinoa without saponin on obesity. We explored the potential therapeutic mechanisms of quinoa using methods such as 16S rRNA, Western blotting, Immunohistochemical (IHC). Our results indicated that quinoa can improve the obese symptoms significantly on HFD mice, as well as aberrant glucose and lipid metabolism. Further analyses suggest that quinoa can regulate microbiota in the colon and have predominantly regulation on Bacteroidetes, Actinobacteria and Desulfovibrio, meanwhile can decrease the F/B ratio and the abundance of Blautia. Contemporaneously, quinoa can upregulate the expression of TGR5 in the colon and brain, as well as GLP-1 in the colon, liver and brain. while downregulate the expression of TLR4 in the colon and liver, as well as markers of ER stress and oxidative stress in livers and serums. Beyond this, tight junctional proteins in colons and brains are also increased in response to quinoa. Therefore, quinoa can effectively reduce obesity and may possibly exert through microbiota-gut-brain-liver interaction mechanisms. IMPORTANCE Gut microbiota has been investigated extensively, as a driver of obesity as well as a therapeutic target. Studies of its mechanisms are predominantly microbiota-gut-brain axis or microbiota-gut-liver axis. Recent studies have shown that there is an important correlation between the gut-brain-liver axis and the energy balance of the body. Our research focus on microbiota-gut-brain-liver axis, as well as influences of quinoa in intestinal microbiota. We extend this study to the interaction between microbiota and brains, and the result shows obvious differences in the composition of the microbiome between the HFD group and others. These observations infer that besides the neurotransmitter and related receptors, microbiota itself may be a mediator for regulating bidirectional communication, along the gut-brain-liver axis. Taken together, these results also provide strong evidence for widening the domain of applicability of quinoa.

Lactobacillus paracasei PS23 improves cognitive deficits via modulating the hippocampal gene expression and the gut microbiota in D-galactose-induced aging mice.

Probiotic supplements are potential therapeutic agents for age-related cognitive deficits. A prior study showed that probiotic Lactobacillus paracasei PS23 (PS23) supplementation delayed age-related cognitive decline in mice. However, the underlying mechanisms remain unclear. This study aimed to investigate the effects of live or heat-killed PS23 (HK-PS23) on cognitive function in D-galactose (D-gal)-induced aging mice and explore the underlying mechanisms. We designed four groups of mice: control, D-gal aging mice, and PS23 supplemented and HK-PS23 supplemented D-gal aging mice. We evaluated memory function and anxiety using Morris water maze and open field tests, respectively. Neural monoamines and activities of superoxide dismutase (SOD) in the hippocampus were evaluated. RNA-seq was used to evaluate hippocampal gene expression profiles in each group, and the composition of the gut microbiota was analyzed. We revealed that PS23 and HK-PS23 supplementation ameliorated D-gal-induced memory deficits and improved motor and anxiety-behaviors in aging mice. In the hippocampus, serotonin levels (5-HT) were increased and the genes involved in neuroplasticity, anti-inflammatory, and antioxidant functions were upregulated in PS23 and HK-PS23 supplemented groups. The gut microbiota showed specific changes. Our results suggest that PS23 and HK-PS23 supplements could ameliorate age-related cognitive decline, possibly by upregulating the genes involved in synaptic plasticity and preventing oxidation and inflammation.

Coagulation Disorders and Thrombosis in COVID-19 Patients and a Possible Mechanism Involving Endothelial Cells: A Review.

Coronavirus disease 2019 (COVID-19) is still an ongoing pandemic worldwide. COVID-19 is an age-related disease with a higher risk of organ dysfunction and mortality in older adults. Coagulation disorders and thrombosis are important pathophysiological changes in COVID-19 infection. Up to 95% of COVID-19 patients have coagulation disorders characterized by an elevated D-dimer, a prolonged prothrombin time, a low platelet count and other laboratory abnormalities. Thrombosis is found in critical cases with an increased risk of death. Endothelial cells are prone to be affected by the novel SARS-CoV-2 and express angiotensin-converting enzyme 2. The evidence, such as the presence of the virus, has been identified, leading to the inflammation and dysfunction. Endothelial cell activation and dysfunction play a pivotal role in the hypercoagulation status in COVID-19 patients. In addition to the direct exposure of subendothelial tissue to blood, Weibel-Palade bodies within the endothelium containing coagulants can be released into the circulation. Endothelial nitric oxide synthase may be impaired, thus facilitating platelet adhesion. Moreover, anti-ß2-glycoprotein I antibodies may also contribute to the coagulopathy in COVID-19 by inducing the upregulation of proinflammatory mediators and adhesion molecules. To conclude, coagulation disorders and thrombosis are vital and predict a poor outcome in COVID-19 patients, especially in severe cases. Endothelial cell activation and dysfunction may play an important role in causing clot formation. More basic and clinical research is warranted to further our understanding of the role of coagulopathy and their possible mechanism in COVID-19 patients.

Predictive value of neutrophil-to-lymphocyte ratio in adult severe tetanus / 中华传染病杂志

Objective:To evaluate the predictive value of neutrophil-to-lymphocyte ratio (NLR) for adult severe tetanus by comparing the NLR in patients with severe and mild tetanus.Methods:A total of 65 adult tetanus patients from the Linyi Central Hospital from January 2009 to December 2020 were enrolled. The patients were divided into two groups including mild group and severe group according to the Ablett classification. The general conditions, laboratory data, and NLR of patients in two group were retrospectively compared using independent samples t test. Multivariate logistic regression analysis was used for the analysis of risk factors for severe tetanus. Spearman correlation method was used for the analysis of the correlation between risk factors and Ablett grades. Receiver operator characteristic (ROC) curve was used for the evaluation of the predictive value. Results:Among the 65 tetanus cases, 34 was in mild group and 31 in severe group. The latency period of patients in severe group was (7.00±3.19) d, which was shorter than that in mild group ((9.18±2.59) d), and the difference was statistically significant ( t=3.03, P=0.004). The NLR of patients in severe group was 4.251±1.936, which was higher than that of mild group (2.533±1.026) , and the difference was statistically significant ( t=4.41, P<0.001). Multivariate logistic regression analysis showed that NLR and latency period were independent risk factors for tetanus severity (odds ratio ( OR)=2.359, 95% confidence interval ( CI) 1.415 to 3.934, P=0.001 and OR=0.748, 95% CI 0.599 to 0.936, P=0.011, respectively). In tetanus patients, the NLR level was positively correlated with Ablett grade ( r=0.644, P<0.001). The ROC curve showed that NLR had good predictive value for adult severe tetanus at a cut-off value of 2.471 (area under the curve (AUC)=0.787), with the sensitivity and specificity of 87.1% and 61.8%, respectively. When combining NLR with latency period (cut-off value of 7.5 d), predictive efficiency was further improved (AUC=0.832) with the sensitivity of 87.1% and specificity of 67.6%( Z=3.43, P<0.001). Conclusions:NLR has a good predictive value for adult severe tetanus, and the predictive efficiency is further improved when combined with latency period.

Oral sulfate solution versus polyethylene glycol for colonoscopy bowel preparation: a randomized controlled study in phase Ⅲ / 中华消化内镜杂志

Objective:To compare the efficacy of oral sulfate solution (OSS) and polyethylene glycol (PEG) electrolyte powder for colonoscopy bowel preparation.Methods:A total of 283 randomized patients from 9 centers in China taking OSS ( n=143) or PEG ( n=140) using two-day split bowel preparation regimen received colonoscopy and assessment. The primary index was the bowel preparation success rate [global Boston bowel preparation scale (BBPS)≥ 6 by independent assessment center]. Secondary indices included BBPS global and segmental scores, investigator satisfaction (5-point Likert scale) with the quality of bowel preparation, patient satisfaction assessed by questionnaires, and patient tolerance assessed by Sharma scale. Compliance and safety were compared between the two groups. Results:The bowel preparation success rates were 100.0% for OSS and 99.3% for PEG [adjusted difference 0.7% (95% CI: -5.3% - 6.7%), P<0.001 for non-inferiority]. The BBPS global score in OSS group was significantly higher than that in PEG group (8.1 VS 7.7, P<0.001). The segment BBPS scores were also higher in OSS group than those in PEG group for all 3 segments (right colon: 2.4 VS 2.3, P=0.002; transverse colon: 2.8 VS 2.7, P=0.018; left colon: 2.8 VS 2.7, P=0.007). Investigator Likert score in the OSS group was significantly higher than that in the PEG group (2.6 VS 2.3, P<0.001). There was no significant difference in compliance between OSS and PEG, except for the second dose (90.9% VS 82.6%, P=0.039). There was no significant difference in patient satisfaction, Sharma score or proportion of patients with tolerance-related symptoms between the two groups. Safety was comparable between the two groups, and all adverse events were mild to moderate. Conclusion:OSS has comparable efficacy with PEG, with higher BBPS scores in all segments, better investigator satisfaction, better compliance in split dose, and comparable patient tolerance and safety.

Non-alcoholic Fatty Liver Disease Affect Efficacy of Immune Checkpoint Inhibitors for Patients with Hepatocellular Carcinoma: Manifestations and Mechanisms / 肿瘤防治研究

The number of patients with the combination of non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) is gradually increasing. In recent years, the immunotherapy has become a new effective way to treat unresectable HCC. The clinical research revealed that the NAFLD could affect the efficacy of immunotherapy treating the HCC. But the mechanism is complicated. The major routes are CD8+PD-1+T cells increasing in NAFLD cause the deficiency in cell proliferation ability; Zn64 activates the anti-tumor immune response of the CSF1; PCSK9 downregulates the LDLR level to suppress the immune response of the CD8+T cells in tumor microenvironment; loss of the immune response induces the liver damage. Researches had indicated that the combination of lenvatinib, PKCa inhibitor, PCSK9 protein inhibition, ferroptosis inducer, and HIF2a small molecule inhibitor can improve the efficacy of immune checkpoint inhibitors for NAFLD-associated hepatocellular carcinoma. This review focuses on the impact of NAFLD on tumor microenvironment and how the NAFLD affect the immune check-point inhibitor effect and to discover the exact mechanism.